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The role of elF3 a Rps3 in stop codon readthrough
Poncová, Kristýna ; Valášek, Leoš (advisor) ; Vopálenský, Václav (referee) ; Krásný, Libor (referee)
Translation represents a highly regulated, interconnected process of protein synthesis in the cell. It could be divided into 4 phases: initiation, elongation, termination, and ribosomal recycling. Our laboratory is involved in in-depth studies of a complex eukaryotic initiation factor 3 protein (eIF3). We are interested not only in revealing its molecular roles in the translational cycle in general but also in specific mechanisms that allow translational regulation according to specific cellular needs. In the budding yeast, the eIF3 is composed of five essential subunits (a/Tif32, b/Prt1, c/Nip1, g/Tif35 and i/Tif34). In mammals, the protein is even more complex, comprising of 12 subunits (a-i, k-m). eIF3 is a key player not only in translation initiation but also in ribosomal recycling and, surprisingly, in translation termination and stop codon readthrough as well. The latter process harbors important clinical potential, as approximately 1/3 of genetically inherited diseases is caused by the presence of a premature termination codon in the protein-coding region. Therefore, understanding the molecular mechanism underlying this phenomenon provides important tools for the targeted and less toxic drug development approaches needed for patient therapy. In this Ph.D. Thesis, I uncovered the role of...
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Role of small ribosomal proteins forming the decoding site in translation.
Hovorková, Zuzana ; Valášek, Leoš (advisor) ; Hálová, Martina (referee)
Translation is one of the key mechanisms occurring in the cell during every second of its existence. It is a very complex process ensured by three main actors: tRNAs, mRNAs and ribosomes. Despite of being thoroughly studied over decades, the understanding of some of its functional aspects is still rather poor. This bachelor thesis focuses on four small ribosomal proteins listed below that are reaching to the decoding centre of the small ribosomal subunit. It raises awareness of the structure and function of uS12, uS19, eS25 and eS30, their evolution, role within the ribosome, and the influence they have on various stages of translation. In particular, this thesis specifically reviews the importance of these four proteins for the stop codon readthrough. This phenomenon occurs when a near-cognate aminoacyl-tRNA or a natural suppressor tRNA wins with eRF1 over the corresponding stop codon and thus protein synthesis is continued resulting in the existence of a longer protein. It summarizes our current knowledge of its origin, molecular details of its mechanism, its existence in different species, benefits and disadvantages it brings to the life of a cell or even an organism, and finally it sums up all available knowledge for potential future use of readthrough in therapeutics. Key words: translation,...
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